Tolerance by Engaging Antigen During Cellular Homeostasis
TEACH
Donor-derived Mesenchymal Stromal Cells, Alemtuzumab, Co-stimulation Blockade and Sirolimus for Tolerance Induction in Adult Kidney Allograft Recipients (ITN062ST)
3 other identifiers
interventional
8
1 country
1
Brief Summary
Anti-rejection medicines, also known as immunosuppressive drugs, are prescribed to organ transplant recipients to prevent rejection of the new organ. Long-term use of these medicines places transplant recipients at higher risk of serious infections and certain types of cancer. The purpose of this study is to determine if:
- it is safe to give mesenchymal stromal cells (MSCs) to kidney transplant recipients, and
- the combination of the immunosuppressive (anti-rejection) study drugs plus the MSCs can allow a kidney transplant recipient to slowly reduce and/or then completely stop all anti-rejection drugs, without rejection of their kidney (renal) allograft, a process called "immunosuppression withdrawal".
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Jul 2018
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 12, 2018
CompletedFirst Posted
Study publicly available on registry
April 20, 2018
CompletedStudy Start
First participant enrolled
July 30, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 6, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
September 16, 2025
CompletedFebruary 13, 2026
February 1, 2026
5.1 years
April 12, 2018
February 10, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Proportion of Participants who Achieve Operational Tolerance
Operational tolerance (to their kidney transplant) defined by participant remaining off all immunosuppression for 52 weeks after completion of Immunosuppression Withdrawal (ISW) with: * No evidence of biopsy-proven allograft rejection after initiation of ISW; * Acceptable renal function, defined as an estimated GFR \> 60 ml/min/1.73cm\^2 calculated using the CKD-EPI equation or a serum creatinine that has increased no more than 25% above baseline, as assessed at the week 52 visit after completion of ISW; * No evidence of sustained transplant renal derived pathologic proteinuria, defined as a persistent protein creatinine ratio of greater than 0.5; and * No Donor Specific Antibodies (DSA) at any time after completion of ISW.
52 weeks after completion of Immunosuppression Withdrawal (ISW)
Secondary Outcomes (11)
Proportion of Participants who Remain Off Immunosuppression
From ISW completion to end of study participation (up to approximately 5 years)
Proportion of Participants who Return to Immunosuppression
From ISW completion to end of study participation (up to approximately 5 years)
Proportion of Participants who Achieve Belatacept Monotherapy
48 weeks from the time of last sirolimus dose
Proportion of Participants who Die
From kidney transplant with alemtuzumab induction to to completion of study (up to approximately 6.5 years)
Time from Transplant to the First Episode of Rejection
From kidney transplantation to completion of study (up to approximately 7 years)
- +6 more secondary outcomes
Study Arms (2)
MSCs 10^4 cells/kg+anti-rejection drugs
EXPERIMENTALThe first dosing cohort of 2 participants will receive 12 infusions of 10\^4 donor-derived Mesenchymal Stromal Cells (MSCs) cells/kg every 4-weeks.
MSCs 10^5 cells/kg+anti-rejection drugs
EXPERIMENTALIf the first 3 infusions of 10\^4 donor-derived Mesenchymal Stromal Cells (MSCs) cells/kg are well tolerated, this cohort of 2 participants will receive 12 infusions of 10\^5 cells/kg every 4-weeks.
Interventions
Per protocol, and, only permitted in cases of sirolimus intolerance.
Per protocol, and, only permitted in cases of sirolimus intolerance.
These MSCs are a cellular product derived from bone marrow and propagated ex vivo using FDA-approved, clinically applicable methods. Their use in kidney transplantation has been associated with a good safety profile.
Alemtuzumab, 30 mg, given once intravenously (IV) over three hours. The infusion of alemtuzumab shall begin within 24 hours of transplantation surgery and shall be given prior to the first dose of belatacept.
Belatacept will be given as an intravenous (IV) infusion of 10mg /kg over 1 hour on transplantation postoperative Day 0, Days 5 and 14, then every 2 weeks (± 2 days) for 5 additional doses.Thereafter, belatacept will be given once every 4 weeks (± 5 days) at 10 mg/kg through 24 weeks post-transplant, then at 5 mg/kg every 4-weeks until the participant is evaluated for belatacept discontinuation.
Rapamune® (sirolimus) (Wyeth Pharmaceuticals Inc., Philadelphia, PA) will be started on transplantation postoperative day 1 at a dose of 2 mg/day orally and adjusted to maintain goal 24-hour trough levels of 8-10 ng/ml. Participants who experience grade 3 sirolimus toxicity will undergo dose reduction.
Per protocol, and, only permitted in cases of sirolimus intolerance.
Eligibility Criteria
You may qualify if:
- Recipient:
- Adult candidates of an human leukocyte antigen (HLA)-non-identical, living-donor kidney transplant:
- Candidates must meet the United Network for Organ Sharing (UNOS) criteria, including laboratory criteria, for transplant listing;
- Evidence of established immunity to Epstein-Barr Virus (EBV) as demonstrated by serologic testing;
- Serological evidence of prior Cytomegalovirus (CMV) infection if donor is CMV positive;
- For women of child bearing potential:
- A negative serum or urine pregnancy test with sensitivity of less than 50 mIU/mL within 72 hours of start of study medication; and
- Agreement to use contraception:
- \--- According to the FDA Office of Women's Health (http://www.fda.gov/birthcontrol), there are a number of birth control methods that are more than 80% effective
- Female recipients of child-bearing potential must consult with their physician and determine the most suitable method(s) from this list to be used for 18 months after the first dose of study therapy.
- Donor:
- Meets institutional selection criteria for organ and bone marrow donation:
- All donors will be screened and tested in accordance with:
- (i) FDA 21 CRF 1271.85 requirements for donors of human cells, tissues, and cellular- and tissue-based products (HCT/P); and
- (ii) standards for living kidney donors testing for infection established by the United Network for Organ Sharing (UNOS).
- +1 more criteria
You may not qualify if:
- Recipient:
- History of any immunodeficiency syndrome (including Human Immunodeficiency Virus-1 (HIV-1) and HIV-2);
- Positive anti-Hepatitis C Virus (HCV) Polymerase Chain Reaction (PCR), anti-Hepatitis C Virus (HBV) PCR, or HBV surface antigen;
- History of malignancy within 5 years of enrollment or any history of hematogenous malignancy or lymphoma; --Exception: Participants with curatively treated non-melanomatous skin cancer or curatively treated cervical carcinoma in situ may be enrolled.
- Underlying renal disease with high likelihood of recurrence, including but not limited to:
- primary focal segmental glomerulosclerosis (FSGS),
- Type I or II membranoproliferative glomerulonephritis (MPGN),
- hemolytic-uremic syndrome and
- thrombotic thrombocytopenic purpura (HUS/TTP) syndrome. ---Subject(s) with end-stage renal disease (ESRD) of unknown etiology and/or has no histologically confirmed diagnosis, may be enrolled into the study as long as there are no clinical signs or symptoms consistent with excluded clinical diagnoses.
- History of active M. tuberculosis:
- Participants with a history of latent M. tuberculosis (LTB) as defined by positive testing for tuberculosis using an approved IGRA blood test, such as QuantiFERON®-Gold TB or T-SPOT-TB assay must:
- have completed treatment for LTB and
- have a negative chest x-ray. ----All participants will undergo IGRA testing for M tuberculosis within 3 months prior to transplant.
- Current or historical evidence of donor-specific antibody;
- Immunosuppressive drug therapy within one year prior to enrollment.
- +17 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- PPD Development, LPcollaborator
- Rho Federal Systems Division, Inc.collaborator
- National Institute of Allergy and Infectious Diseases (NIAID)lead
- Immune Tolerance Network (ITN)collaborator
Study Sites (1)
Duke University Health System
Durham, North Carolina, 27710, United States
Related Links
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Allan D. Kirk, M.D., Ph.D.
Duke University Medical Center: Transplantation
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 12, 2018
First Posted
April 20, 2018
Study Start
July 30, 2018
Primary Completion
September 6, 2023
Study Completion
September 16, 2025
Last Updated
February 13, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will share
- Time Frame
- The aim is to share data available to the public within 24 months upon completion of the study.
- Access Criteria
- ImmPort public data access.
The plan is to share data upon completion of the study in ImmPort, a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.